Advertisement

ALG3 Mannosyltransferase

  • Jonne H. Helenius
  • Claude A. Jakob

Abstract

N-Linked glycosylation is an essential eukaryotic protein modification. An oligosaccharide consisting of 14 sugar residues is synthesized at the endoplasmic reticulum (ER) membrane before being transferred to a protein (Kornfeld and Kornfeld 1985; Varki 1996; Burda and Aebi 1999). Dolichol phosphate is used as a lipid carrier for the synthesis, which is initiated by the addition of phospho-GlcNAc forming GlcNAc- pyrophosphate-dolichol (GlcNAc-PP-Dol). This is followed, in order, by additions of another GlcNAc, nine mannose, and three glucose residues. On the cytoplasmic side of the ER, activated sugars (UDP-GlcNAc and GDP-Man) are the donors for the two GlcNAc and first five mannose additions, respectively. The Man5GlcNAc2-PP-Dol is then translocated across the membrane into the ER lumen, where dolichol-phosphate- mannose-dependent mannosyltransferases sequentially add four mannose residues. (For further information on Dol-P-Man, see Chapter 78). The synthesis is completed by the transfer of three glucose residues from Dol-P-Glc to the oligosaccharide. (For a description of Dol-P-Glc-dependent transferases, see Chapter 82). The Glc3Man9GlcNAc2 oligosaccharide is transferred to nascent glycoproteins by the oligosaccharyltransferase complex (see Chapter 83).

Keywords

Killer Toxin Mannose Residue Endoplasmic Reticulum Lumen ALC3 Gene Dolichol Phosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aebi M, Gassenhuber J, Domdey H, te Heesen S (1996) Cloning and Characterization of the ALG3 gene of Saccharomyces cerevisiae, Glycobiology 6:439–444PubMedCrossRefGoogle Scholar
  2. Banerjee DK (1989) Amphomycin inhibits mannosylphosphoryldolichol synthesis by forming a complex with dolichylmonophosphate. J Biol Chem 264:2024–2028PubMedGoogle Scholar
  3. Burda P, Aebi M (1999) The dolichol pathway of N-glycosylation. Biochim Biophys Acta 1426:239–257PubMedCrossRefGoogle Scholar
  4. Burda P, Jakob CA, Beinhauer J, Hegemann JH, Aebi M (1999) Ordered assembly of the asymmetrically branched lipid-linked oligosaccharide in the endoplasmic reticulum is ensured by the substrate specificity of the individual glycosyltransferases. Glycobiology 9:617–625PubMedCrossRefGoogle Scholar
  5. Burda P, te Heesen S, Aebi M (1996) Stepwise assembly of the lipid-linked oligosaccharide in the endoplasmic reticulum of Saccharomyces cerevisiae: identification of the ALG9 gene encoding a putative mannosyl transferase. Proc Natl Acad Sci USA 93:7160–7165PubMedCrossRefGoogle Scholar
  6. Cipollo JF, Trimble RB (2000) The accumulation of Man(6)GlcNAc(2)-PP-dolichol in the Saccharomyces cerevisiae Δalg9 mutant reveals a regulatory role for the Alg3p α1,3-Man middle-arm addition in downstream oligosaccharide-lipid and glycoprotein glycan processing. J Biol Chem 275:4267–4277PubMedCrossRefGoogle Scholar
  7. Conzelmann A, Fankhauser C, Puoti A, Desponds C (1991) Biosynthesis of glycophosphoinositol anchors in Saccharomyces cerevisiae. Cell Biol Int Rep 15:863–873PubMedCrossRefGoogle Scholar
  8. Dean N (1994) Yeast glycosylation mutants are sensitive to aminoglycosides. Proc Natl Acad Sci USA 92:1287–1291CrossRefGoogle Scholar
  9. Elbein AD (1991) Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing. FASEB J 5:3055–3063PubMedGoogle Scholar
  10. Ellgaard L, Molinari M, Helenius A (1999) Setting the standards: quality control in the secretory pathway. Science 286:1882–1888PubMedCrossRefGoogle Scholar
  11. Huffaker TC, Robbins PW (1981) Temperature-sensitive yeast mutants deficient in asparagine-linked glycosylation. J Biol Chem 257:3203–3210Google Scholar
  12. Huffaker TC, Robbins PW (1983) Yeast mutants deficient in protein glycosylation. Proc Natl Acad Sci USA 80:7466–7470PubMedCrossRefGoogle Scholar
  13. Kasahara S, Yamada H, Mio T, Shiratori Y, Miyamoto C, Yabe T, Nakajima T, Ichishima E, Furuichi Y (1994) Cloning of the Saccharomyces cerevisiae gene whose overexpres-sion overcomes the effects of HM-1 killer toxin, which inhibits beta-glucan synthesis. J Bacteriol 176:1488–1499PubMedGoogle Scholar
  14. Korner C, Knauer R, Stephani U, Marquardt T, Lehle L, von Figura K (1999) Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase. EMBO J 18:6816–6822PubMedCrossRefGoogle Scholar
  15. Kornfeld R, Kornfeld S (1985) Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 54:631–664PubMedCrossRefGoogle Scholar
  16. Kukuruzinska MA, Lennon-Hopkins K (1999) ALG gene expression and cell cycle progression. Biochim Biophys Acta 1426:359–372PubMedCrossRefGoogle Scholar
  17. Kurzik-Dumke U, Kaymer M, Gundacker D (1997) Gene within a gene configuration and expression of the Drosophila melanogaster genes lethal(2) neighbour of tid [1(2)not] and lethal (2) relative of tid. Genetics 200:45–58Google Scholar
  18. Orlean P (1990) Dolichol phosphate mannose synthase is required in vivo for glycosyl phosphatidylinositol membrane anchoring, O mannosylation, and N glycosylation of protein in Saccharomyces cerevisiae. Mol Cell Biol 10:5796–5805PubMedGoogle Scholar
  19. Orlean P (1994) DPM1. In: Book Rothblatt J, Novick P, Stevens T (eds) Guidebook to the secretory pathway. Oxford University Press, Oxford, pp 54–56Google Scholar
  20. Orlean P (2000) Congenital disorders of glycosylation caused by defects in mannose addition during N-linked oligosaccharide assembly. J Clin Invest 105:131–132PubMedCrossRefGoogle Scholar
  21. Orlean P, Albright C, Pobbins PW (1988) Cloning and sequencing of the yeast gene for dolichol phosphate mannose synthase, an essential protein. J Biol Chem 263:17499–17507PubMedGoogle Scholar
  22. Ram AF, Wolters A, Ten HR, Klis FM (1994) A new approach for isolating cell wall mutants in Saccharomyces cerevisiae by screening for hypersensitivity to calcofluor white. Yeast 10:1019–1030PubMedCrossRefGoogle Scholar
  23. Rush J, Waechter CJ (1998) Topological studies on the enzymes catalyzing the biosynthesis of Glc-P-dolichol and the triglucosyl cap of Glc3Man9GlcNAc2-P-P-dolichol in microsomal vesicles from pig brain: use of the processing glucosidases I/II as latency markers. Glycobiology 8:1207–1213PubMedCrossRefGoogle Scholar
  24. Schachter H (1995) Biosynthesis. In: Book Montreuil J, Schachter H, Vliegenhart JFG (eds) Glycoproteins. Elsevier Science, Amsterdam, pp 123–126CrossRefGoogle Scholar
  25. Sharma CB, Kausthal GP, Pan YT, Elbein AD (1990) Purification and characterization of dolichyl-P-mannose:Man5(GlcNAc)2-PP-dolichol mannosyltransferase. Biochemistry 29:8901–8907PubMedCrossRefGoogle Scholar
  26. Shimma Y, Nishikawa A, bin Kassim B, Eto A, Jigami Y (1997) A defect in GTP synthesis affects mannose outer chain elongation in Saccharomyces cerevisiae. Mol Gen Genet 256:469–480PubMedCrossRefGoogle Scholar
  27. Varki A (1996) “Unusual” modifications and variations of vertebrate oligosaccharides: are we missing the flowers for the trees? Glycobiology 6:707–710PubMedCrossRefGoogle Scholar
  28. Verostek MF, Atkinson PH, Trimble RB (1991) Structure of Saccharomyces cerevisiae alg3, sec 18 mutant oligosaccharides. J Biol Chem 266:5547–5551PubMedGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Jonne H. Helenius
    • 1
  • Claude A. Jakob
    • 1
  1. 1.Insitute for MicrobiologyETH ZürichZürichSwitzerland

Personalised recommendations